Carboxylated polymers, such as poly(acrylic) acid, are known to be effective as bioadhesive compositions, but their use is limited owing to problems associated with mucosa irritation. To overcome these problems, it is known to blend these polymers with other materials such as starch (as described in U.S. Pat. No. 5,643,603 (Janssen Pharmaceuticals)).
Known bioadhesive compositions are described in WO 98/22097 (Bio Advances); EP 410,696 (E. R. Squibb); U.S. Pat. No. 5,643,603 (Janssen Pharmaceuticals); and U.S. Pat. No. 4,915,948 (Warner-Lambert).
WO 98/22097 refers to compositions of poly(acrylic) acid and a polar polymer or monomer produced under conditions that ensure hydrogen bonding interactions, rather than cross-linking, occur.
EP 410,696 discloses a mucoadhesive delivery system comprising poly(acrylic) acid crosslinked with 1 percent to 20 percent by weight of a polyhydroxy compound and a therapeutically effective amount of a drug. This invention is concerned with the use of low molecular weight polyhydroxy compounds.
U.S. Pat. No. 5,643,603 describes a bioadhesive carrier composition which is a tablet formulated from pregelatinized starch, synthetic polymer such as poly(acrylic) acid and a drug. The pregelatinized starch is used as a substitute adhesive allowing for lower loading of poly(acrylic) acid to reduce corresponding irritation effects.
U.S. Pat. No. 4,915,948 refers to a tablet with bioadhesive properties prepared from a blend of xanthan gum and/or a pectin combined with a solid polyol. The blend is prepared without any form of heating.
Prior art methods of crosslinking polycarboxylated polymers with polysaccharides include the method described in U.S. Pat. No. 5,895,804 (National Starch and Chemical) wherein polysaccharide and polycarboxylated polymer are combined under conditions effective to induce crosslinking of the polycarboxylated polymer.
None of the above patents or references provide a method of preparing bioadhesive compositions having the high loading of poly(acrylic) acid and corresponding adhesion and low irritation properties described in this invention.